This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The need for iodide in biology is almost exclusively limited to its role in thyroid hormones. Recycling of thyroidal iodide is critical for maintaining proper hormone levels. The flavoprotein iodotyrosine deiodinase (IYD) salvages iodide from byproducts (mono- and diiodotyrosine, MIT and DIT) of thyroid hormone biosynthesis. The original proposal for the deiodination mechanism of IYD included a nucleophilic attack of the iodo group by an active site cysteine. Although this proposed mechanism has strong precedence, site-directed mutagenesis proved this wrong. Structures of IYD with bound MIT and DIT were sought to elucidate the enzymatic mechanism of this enzyme.